A5058915340- Vector-borne infectious diseases
- Viral Infections and Vectors
- Vector-Borne Animal Diseases
- Insect symbiosis and bacterial influences
- Mosquito-borne diseases and control
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Dermatological diseases and infestations
- Insect and Pesticide Research
- Oral microbiology and periodontitis research
- Genomics and Phylogenetic Studies
- interferon and immune responses
- Immune Cell Function and Interaction
- Parasites and Host Interactions
- Inflammasome and immune disorders
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Clostridium difficile and Clostridium perfringens research
- Leptospirosis research and findings
- Plant and Fungal Interactions Research
- Bartonella species infections research
- Neuropeptides and Animal Physiology
- Heat shock proteins research
- Infective Endocarditis Diagnosis and Management
- Cellular transport and secretion
- Research on Leishmaniasis Studies
Tufts University
2016-2025
Tufts Medical Center
2009-2021
Boston University
2001-2012
University of South Florida
2007
St. Elizabeth's Medical Center
2004
New York Medical College
2003
Yale University
2003
It is controversial whether prolonged antibiotic treatment effective for patients in whom symptoms persist after the recommended acute Lyme disease.We conducted two randomized trials: one 78 who were seropositive IgG antibodies to Borrelia burgdorferi at time of enrollment and other 51 seronegative. The received either intravenous ceftriaxone, 2 g daily 30 days, followed by oral doxycycline, 200 mg 60 or matching placebos. Each patient had well-documented, previously treated disease but...
Background : It is controversial whether additional antibiotic treatment will improve cognitive function in patients with post-treatment chronic Lyme disease (PTCLD). Objective To determine therapy improves two randomized double-blind placebo-controlled studies of PTCLD. Methods A total 129 a physician-documented history from three study sites the northeast United States were studied. Seventy-eight seropositive for IgG antibodies against Borrelia burgdorferi , and 51 seronegative. Patients...
Abstract Background Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with periodontal disease onset and progression. Genetic tools for the manipulation of bacterial genomes allow in-depth mechanistic studies metabolism, physiology, interspecies host-pathogen interactions. Analysis essential genes, protein-coding sequences necessary survival P. by transposon mutagenesis has not previously been attempted due to limitations available systems organism. We adapted...
Background. Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using natural tick vector (Ixodes scapularis). No convincing evidence exists for persistence viable spirochetes recommended courses in humans. We determined safety I. scapularis larvae B. burgdorferi infection Methods. Laboratory-reared larval ticks were placed on 36 subjects allowed to feed repletion. Ticks...
ABSTRACT The contribution of Toll-like receptors (TLRs) to phagocytosis Borrelia burgdorferi has not been extensively studied. We show that bone marrow-derived macrophages (BMDM) from MyD88 −/− mice or Raw cells transfected with a dominant-negative were unable efficiently internalize B. burgdorferi. Knockouts TLR2 and TLR9 knockdown TLR5 by small interfering RNA produced no defects in . Production inflammatory cytokines was greatly diminished BMDM but only partially affected unaffected BMDM....
Abstract A growing global health concern, Lyme disease has become the most common tick-borne in United States and Europe. Caused by bacterial spirochete Borrelia burgdorferi sensu lato (sl), this can be debilitating if not treated promptly. Because diagnosis is challenging, prevention remains a priority; however, previously licensed vaccine no longer available to public. Here, we designed six component that elicits antibody (Ab) responses against all strains commonly cause humans. The outer...
It has been postulated that the vls system of Lyme disease spirochetes contributes to immune evasion through antigenic variation. While it is clear vlsE undergoes sequence change within its variable regions at a high frequency during early stages infection, definitive role in not demonstrated. In this report we assessed murine and human humoral response recombinant (r)-VlsE variants originally arose infection mice. Immunoblot analyses r-VlsE were conducted by using serum samples collected...
We studied the binding of plasminogen to Borrelia burgdorferi, a spirochete which causes Lyme disease and produces no endogenous proteases digest extracellular matrix proteins. Using 125I-labeled plasminogen, we demonstrated that B. burgdorferi bound human this was inhibitable with unlabeled plasminogen. by also inhibited lysine analog epsilon-aminocaproic acid. There significant difference in Glu- or Lys-plasminogen burgdorferi. Binding similar low-passage (infectious) high-passage...
Borrelia burgdorferi is an invasive spirochete that can cause acute and chronic infections in the skin, heart, joints, central nervous system of infected mammalian hosts. Little understood about where bacteria encounter strongest barriers to infection how different components host immune influence population as progresses. To identify bottlenecks a murine host, we utilized Tn-seq monitor composition mixed populations B. during infection. Both wild-type mice lacking Toll-like receptor adapter...
ABSTRACT TRIF is an adaptor molecule important in transducing signals from intracellularly signaling Toll-like receptor 3 (TLR3) and TLR4. Recently, TLR2 was found to signal intracellular compartments. Using a synthetic ligand for TLR2/1 heterodimers, as well Borrelia burgdorferi , which strong activator of TLR2/1, we that can utilize TRIF. Unlike by other TLRs, TLR2-mediated dependent on the presence another molecule, MyD88. However, unlike MyD88 deficiency, deficiency does not result...
Abstract Borrelia burgdorferi stimulates a robust inflammatory response at sites of localization. Binding borrelial lipoproteins to TLR-2 is one pathway important in the host B. burgdorferi. However, while clearly control infection, inflammation actually worsened absence or shared TLR adapter molecule, MyD88, suggesting that there are alternative pathways regulating inflammation. Integrins cell surface receptors play an role communications and can activate signaling pathways. In this study,...
Borrelia burgdorferi, the causative agent of Lyme disease, activates multiple signalling pathways leading to induction pro-inflammatory mediators at sites inflammation. Binding B. burgdorferi integrin alpha(3)beta(1) on human chondrocytes release several mediators, but protein that binds and elicits this response has remained unknown. A search genome for a canonical binding motif, RGD (Arg-Gly-Asp) tripeptide, revealed candidate ligands integrins. In study we show one these candidates,...
Background Toll-like receptor (TLR)-2/TLR1 heterodimers recognize bacterial lipopeptides and initiate the production of inflammatory mediators. Adaptors co-receptors that mediate this process, as well mechanisms by which these adaptors function, are still being discovered. Methodology/Principal Findings Using shRNA, blocking antibodies, fluorescent microscopy, we show U937 macrophage responses to TLR2/1 ligand, Pam3CSK4, dependent upon an integrin, α3β1. The mechanism for integrin α3β1...
Borrelia burgdorferi maintains a complex life cycle between tick and vertebrate hosts. Although some genes have been identified as contributing to bacterial adaptation in the different hosts, list is incomplete. In this manuscript, we report first use of transposon mutagenesis combined with high-throughput sequencing (Tn-seq) B. burgdorferi. We utilize technique investigate mechanisms carbohydrate utilization role metabolism during mouse infection. performed genetic fitness analyses identify...
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is exposed to reactive oxygen and nitrogen species (ROS RNS) both tick vector vertebrate reservoir hosts. B. burgdorferi contains a limited repertoire canonical oxidative stress response genes, suggesting that novel gene functions may be important for protection against ROS or RNS exposure. Here, we use transposon insertion sequencing (Tn-seq) conduct an unbiased search genes involved resistance nitric oxide, hydrogen...
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive complete its enzootic B. burgdorferi adapts to diverse hosts by regulating genes required for survival specific environments. Here we describe first ever use transposon insertion sequencing (Tn-seq) identify host. We found that insertions into 46 resulted loss recovery mutants from larval Ixodes ticks....